PROJECT SUMMARY Despite the remarkable overall progress in reducing maternal mortality worldwide, preeclampsia continues to be a major cause of maternal death, infant prematurity, and low birth weight in Africa. Preeclampsia is especially high in Ghana occurring in 7.9% of term pregnancies. Preeclampsia presents during mid- pregnancy with hypertension and proteinuria, and frequently includes kidney, liver, hematological, and neurological dysfunction, as well as reduced fetal growth. Kidney disease is strongly linked to preeclampsia and may have a causative impact through abnormal vascular responses to placentation and endothelial dysfunction. A genetic predisposition to preeclampsia has long been suspected, but is essentially unstudied in Africa. As a candidate gene for preeclampsia association, apolipoprotein L1 (APOL1) is a known risk factor for end-stage and chronic kidney disease. APOL1 high-risk variants are present at very high frequency in the same West African populations that also show high levels of preeclampsia. The proposed research will (1) determine maternal and infant APOL1 risk variants and their association with preeclampsia, (2) provide novel insights into genetic factors that impact maternal risk and perinatal outcomes, and (3) create a West African preeclampsia genetics research infrastructure, based on a characterized patient cohort (700 cases and 700 controls) and a bio-specimen repository. The project will determine the association of APOL1 variants in mothers and infants, with preeclampsia frequency and neonatal health. The expression of APOL1 mRNA, stratified by APOL1 variant status, will be examined in placentas, in the preeclampsia patients/control population. Finally, the incidence of kidney disease, APOL1 variation, hypertension, and preeclampsia will be examined in the clinical population. The proposed training and research will be performed in Accra, Ghana, at the Korle Bu Teaching Hospital, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, and the Noguchi Memorial Institute of Medical Research. The trainee, Dr. Charlotte Osafo (MBChB), will be supervised by a mentoring team of senior physicians and scientists in Ghana, the United States, and Canada. The mentoring team has extensive research expertise in maternal health, hypertension, chronic kidney disease, clinical studies research, and human genetics. The overall research objective is to uncover the interaction of population genetic variation with preeclampsia, and maternal and infant health outcomes.